The Role of Liver Biopsy in Drug-Induced Liver Injury
- 13 Downloads
Purpose of Review
This review presents the current understanding of the role played by liver biopsy in the diagnosis and management of drug-induced liver injury (DILI).
While liver biopsy remains an optional procedure in the evaluation of DILI, it has the potential to provide detailed information about the state of the liver. Recent histological surveys of DILI provide a framework for categorizing the patterns of injury that may be seen. Pattern information can be used to distinguish DILI from other potential causes of injury, both other acute injuries as well as pre-existing injury. The pattern of injury is related to differential diagnosis and in some cases can suggest a mechanism of injury. The character and severity of the injury could potentially be used in clinical decision-making. Examples of the use of liver biopsy in the context of DILI encountered in clinical trials are provided which highlight these points.
Liver biopsy may be a useful tool in DILI evaluation, particularly in complex clinical situations and clinical trials with experimental therapies.
KeywordsHepatotoxicity Acute hepatitis Cholestasis Checkpoint inhibitor Clinical trial
Dr. Kleiner prepared the manuscript, including all figures and tables.
This review was financially supported by the Intramural Research Program of the NIH, National Cancer Institute.
Compliance with Ethical Standards
Conflict of Interest
David E. Kleiner declares no potential conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.Uetrecht J, Zahid N, Shear NH, Biggar WD. Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells. J Pharmacol Exp Ther. 1988;245(1):274–9.Google Scholar
- 6.Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, Williams & Wilkins; 1999.Google Scholar
- 8.•• Wang T, Zhao X, Shao C, Ye L, Guo J, Peng N, et al. A proposed pathologic sub-classification of drug-induced liver injury. Hepatol Int. 2019. https://doi.org/10.1007/s12072-019-09940-9 Adds a new histologic classification system that may be better fitted for DILI cases from Asia .
- 9.Philips CA, Paramaguru R, Joy AK, Antony KL, Augustine P. Clinical outcomes, histopathological patterns, and chemical analysis of Ayurveda and herbal medicine associated with severe liver injury-a single-center experience from southern India. Indian J Gastroenterol. 2018;37(1):9–17. https://doi.org/10.1007/s12664-017-0815-8.CrossRefGoogle Scholar
- 16.• Czeczok TW, Van Arnam JS, Wood LD, Torbenson MS, Mounajjed T. The almost-normal liver biopsy: presentation, clinical associations, and outcome. Am J Surg Pathol. 2017;41(9):1247–53. https://doi.org/10.1097/PAS.0000000000000881 Careful examination of the etiological challenges presented by biopsies with minimal findings . CrossRefGoogle Scholar
- 18.Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, et al. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015;110(10):1450–9. https://doi.org/10.1038/ajg.2015.283.CrossRefGoogle Scholar
- 19.• Bonkovsky HL, Kleiner DE, Gu J, Odin JA, Russo MW, Navarro VM, et al. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology. 2017;65(4):1267–77. https://doi.org/10.1002/hep.28967 Detailed description of histology and clinical outcomes for vanishing bile duct syndrome due to DILI. CrossRefGoogle Scholar
- 21.Kleiner DE, Gaffey MJ, Sallie R, Tsokos M, Nichols L, McKenzie R, et al. Histopathologic changes associated with fialuridine hepatotoxicity. Mod Pathol. 1997;10(3):192–9.Google Scholar
- 24.Lewis W, Levine ES, Griniuviene B, Tankersley KO, Colacino JM, Sommadossi JP, et al. Fialuridine and its metabolites inhibit DNA polymerase gamma at sites of multiple adjacent analog incorporation, decrease mtDNA abundance, and cause mitochondrial structural defects in cultured hepatoblasts. Proc Natl Acad Sci U S A. 1996;93(8):3592–7.CrossRefGoogle Scholar
- 30.•• Zen Y, Yeh MM. Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury. Mod Pathol. 2018;31(6):965–73. https://doi.org/10.1038/s41379-018-0013-y Provides histologic description of a growing class of agents that can cause DILI felt to be immune mediated. CrossRefGoogle Scholar
- 32.Guidelines for diagnosis of therapeutic drug-induced liver injury in liver biopsies. Lancet. 1974;1(7862):854–7.Google Scholar